title: The anti-adipogenic effect of PGRN on porcine preadipocytes involves ERK1,2 mediated PPARγ phosphorylation.
abstract: Recent researches indicate that PGRN is closely related to diabetes and is regarded as a novel adipokine associated with obesity development, affecting adipocyte biology. In the present study, we investigated the effects and mechanisms of PGRN on porcine preadipocytes differentiation. Porcine preadipocytes were induced to differentiation with the addition of lentivirius-expressed PGRN shRNA at the early or late stage of induction period, and in the presence or absence of recombinant PGRN protein. The effects of PGRN on adipogenic genes expression and ERK activation were investigated. At the early stage of induction, knockdown of PGRN promoted differentiation, evidenced by enhanced lipid accumulation, upregulation of adipocyte markers, as well as master adipogenic transcription factors, PPARγ and C/EBPα. While, decreasing PGRN expression at the late stage of induction (day 3) had no effect on differentiation. These results suggested that PGRN functions in the early adipogenic events. Conversely, porcine preadipocytes differentiation was impaired by MDI and recombinant PGRN protein induction, the expressions of adipocyte markers were decreased. Further studies revealed that PGRN can specifically facilitate ERK1,2 activation, and this activation can be abolished by U0126. Moreover, PPARγ phosphorylation at serine 112 site was increased by PGRN treatment, which could reduce the transcriptional activity of PPARγ. We conclude that PGRN inhibits adipogenesis in porcine preadipocytes partially through ERK activation mediated PPARγ phosphorylation.
authors.affiliation: Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Jia
authors.initials: J
authors.lastname: Cheng
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Song
authors.forename: Xinjian
authors.initials: X
authors.lastname: Li
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yin
authors.initials: Y
authors.lastname: Mai
authors.forename: Weijun
authors.initials: W
authors.lastname: Pang
authors.forename: Xin'e
authors.initials: X
authors.lastname: Shi
authors.forename: Gongshe
authors.initials: G
authors.lastname: Yang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003433:Crosses, Genetic; D003470:Culture Media / Q000494:pharmacology; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D034421:Sus scrofa; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D003470:Culture Media; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D010768:Phosphoserine; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases